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Optimal cardiac dose constraints in breast cancer (BC) patients undergoing postoperative intensity-modulated radiation therapy (IMRT) are unclear, although as low as possible is recommended. This trial proposes serial cardiac dose constraint to optimize cardiac safety. Postoperative BC patients eligible for anthracycline/taxanes-based chemotherapy or HER2-targeted therapy were randomized to cardiac safety arm with prespecified mean heart dose (MHD) (≤6 Gy), V30 (≤20%), and V10 (≤50%) constraints, or to a control arm with in-house protocol (mainly MHD ≤8 Gy). The primary endpoint was cumulative incidence of newly onset cardiac events within 1-year post-RT. An exploratory analysis examined the relationship between whole heart dose metrics and those of substructures. Of 199 participants, 93 were in the cardiac safety and 106 in the control arm. The cardiac safety group showed lower MHD, V10, and V30. The 1-year cardiac event incidence was slightly lower in the cardiac safety group (19.4%) compared to controls (24.9%). The LVEF and diastolic dysfunction rates were 0% and 5.4% in the study arm, and 1.9% and 8.8% in the control arm, respectively. The LAD, LV, and RV received the highest doses for left-sided patients. For right-sided patients, RA, RCA, and RV were most irradiated. The MHD, V10, and Dmax of heart significantly correlated with all substructure doses in either laterality. Our study supports the early cardiac safety profile using IMRT in BC patients receiving cardiac-toxic systemic therapy, with serial cardiac dose constraints. Combined constraints on MHD and dose-volume parameters are representative of the cardiac substructure dose., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

With the development of metalloimmunology, the potential of platinum drugs in cancer immunotherapy has attracted extensive attention. Although immunochemotherapy combining PD-1/PD-L1 antibodies with platinum drugs has achieved great success in the clinic, combination therapy commonly brings new problems. Herein, we have developed a platinum-metformin conjugate as a promising alternative to antibody-based PD-L1 inhibitors, not only disrupting PD-1/PD-L1 axis on cell surface but also down-regulating the total PD-L1 levels in non-small cell lung cancer (NSCLC) cells comprehensively, thus achieving highly efficient immunochemotherapy by a single small molecule. Mechanism studies demonstrate that Pt-metformin conjugate can selectively accumulate in lysosomes, promote lysosomal-dependent PD-L1 degradation via the AMPK-TFEB pathway, and modulate the upstream regulatory proteins related to PD-L1 expression (e.g. HIF-1α and NF-κB), eventually decreasing the total abundance of PD-L1 in NSCLC, overcoming tumor hypoxia, and activating anti-tumor immunity in vivo. This work suggests an AMPK-mediated lysosomal degradation pathway of PD-L1 for the first time and provides a unique design perspective for the development of novel platinum drugs for immunochemotherapy., (© 2024 Wiley-VCH GmbH.)

Background: Gallbladder cancer (GBC) was once considered a contraindication for laparoscopic surgery, but it is becoming more common to use laparoscopic surgery for GBC treatment. The aim of this study was to analyze the long- and short-term outcomes of patients with more advanced T-staged GBC treated with curative intent as defined by the National Comprehensive Cancer Network (NCCN) after laparoscopic resection (LR) versus open resection (OR)., Methods: A multicenter database was used to select consecutive GBC patients treated with curative-intent resection as defined by the NCCN between 2016 and 2020. The patients were divided into the LR group and the OR group. Propensity score matching (PSM) was used to eliminate selection bias. The endpoints were overall survival (OS), progression-free survival (PFS), and short-term outcomes. Risk factors that were independently associated with OS and PFS were identified., Results: Of 626 GBC patients treated with curative-intent resection, after PSM, 51 patients were in the LR group and 153 patients were in the OR group. The LR group had more patients who were suitable to receive adjuvant chemotherapy (AC), a longer operation time, more harvested lymph nodes, and a lower overall morbidity rate. The rates of OS and PFS were not significantly different between the two groups. AC was independently associated with better OS and PFS., Conclusions: The overall morbidity of GBC patients after LR was lower, but the long-term outcomes between LR and OR were not significantly different. The GBC patients treated with LR were more likely to receive AC, and the use of AC after curative-intent resection of GBC helped achieve better long-term survival outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-518/coif). W.Y.L. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Nitrous oxide (N 2 O) is a potent greenhouse gas with various production pathways. N 2 O reductase (N 2 OR) is the primary N 2 O sink, but the distribution of its gene clades, typically nosZ I and atypically nosZ II, along urbanization gradients remains poorly understood. Here we sampled soils from forests, parks, and farmland across eight provinces in eastern China, using high-throughput sequencing to distinguish between two N 2 O-reducing bacteria clades. A deterministic process mainly determined assemblies of the nosZ I communities. Homogeneous selection drove nosZ I deterministic processes, and both homogeneous and heterogeneous selection influenced nosZ II. This suggests nosZ II is more sensitive to environmental changes than nosZ I, with significant changes in community structure over time or space. Ecosystems with stronger anthropogenic disturbance, such as urban areas, provide diverse ecological niches for N 2 O-reducing bacteria (especially nosZ II) to adapt to environmental fluctuations. Structural equation modeling (SEM) and correlation analyses revealed that pH significantly influences the community composition of both N 2 O-reducing bacteria clades. This study underscores urbanization's impact on N 2 O-reducing bacteria in urban soils, highlighting the importance of nosZ II and survival strategies. It offers novel insights into the role of atypical denitrifiers among N 2 O-reducing bacteria, underscoring their potential ecological importance in mitigating N 2 O emissions from urban soils.

Background: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients., Methods: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS., Results: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003)., Conclusions: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Fully considering the mechanical and photoelastic anisotropies of monocrystalline silicon, the impacts of spatial symmetries on the stimulated Brillouin scatterings (SBSs) in nanoscale suspended silicon waveguides are studied theoretically and numerically based on group theory. First, starting from an assumption that the principal material coordinate system can be arbitrarily orientated in a waveguide with fixed geometry, the silicon waveguides are systematically classified into a number of point groups according to their spatial symmetry features. Thereafter, the symmetry characteristics of physical fields and SBS opto-mechanical coupling characteristics in the silicon waveguides belonging to different point groups are further examined, and the major new findings can be summarized as follows: The SBS opto-mechanical couplings in several kinds of silicon waveguides with certain nontrivial symmetry features exhibit relatively predictable behaviors in that the opto-mechanical coupling coefficients can be deterministically vanishing or nonvanishing under very few constraints, which can thus serve as general symmetry selection rules for SBSs in suspended silicon waveguides. The results obtained in the present study could be a useful theoretical reference for the design of novel SBS-active silicon photonic devices.

The causal agent of rice bacterial leaf blight (BLB) is Xanthomonas oryzae pv. oryzae (Xoo), which causes serious damage to rice, leading to yield reduction or even crop failure. Brevibacillus laterosporus SN19-1 is a biocontrol strain obtained by long-term screening in our laboratory, which has a good antagonistic effect on a variety of plant pathogenic bacteria. In this study, we investigated the efficacy and bacterial inhibition of B. laterosporus SN19-1 against BLB to lay the theoretical foundation and research technology for the development of SN19-1 as a biopesticide of BLB. It was found that SN19-1 has the ability to fix nitrogen, detoxify organic phosphorus, and produce cellulase, protease, and siderophores, as well as IAA. In a greenhouse pot experiment, the control efficiency of SN19-1 against BLB was as high as 90.92%. Further investigation of the inhibitory mechanism of SN19-1 on Xoo found that the biofilm formation ability of Xoo was inhibited and the pathogenicity was weakened after the action of SN19-1 sterile supernatant on Xoo. The activities of enzymes related to respiration and the energy metabolism of Xoo were significantly inhibited, while the level of intracellular reactive oxygen species was greatly increased. Scanning electron microscopy observations showed folds on the surface of Xoo. A significant increase in cell membrane permeability and outer membrane permeability and a decrease in cell membrane fluidity resulted in the extravasation of intracellular substances and cell death. The results of this study highlight the role of B. laterosporus SN19-1 against the pathogen of BLB and help elucidate the underlying molecular mechanisms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi-autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi-targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein administration also features a good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down-regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi-dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi-targeted Pt complex that can trigger Golgi stress-mediated dual-regulation of autophagic flux and autophagy-apoptosis crosstalk for highly efficient cancer therapy., (© 2023 Wiley-VCH GmbH.)

The subjective measurement of the dynamic perception of sweetness is a problem in food science. Herein, the rapid interactions of sugars and sugar alcohols with sweet taste receptors on living cells on a millisecond timescale were studied via stopped-flow fluorescence spectroscopy. According to the rapid-kinetic parameters, sweeteners were divided into two groups. Sweeteners in group I disrupted the hydrogen bond network structure of water, and the apparent rate constant ( k obs ) was in the range of 0.45-0.6 s -1 . Sweeteners in group II promoted the hydrogen bond formation of water, and the k obs was mostly in the range of 0.6-0.75 s -1 . For most sweeteners, the k obs of cell responses was negatively correlated with the apparent specific volume of sweeteners. The differences in the cellular responses may be attributed to the disturbance in the water structure. Experimental results showed that the kinetic parameters of sweet cell responses reflected the dynamic perception of sweetness. Rapid kinetics, solution thermodynamic analysis, and water structure analysis enriched the physicochemical study of the sweetness mechanism and can be used to objectively evaluate the dynamic perception of sweetness.

Purpose: To integrate digital dynamic smile aesthetic simulation (DSAS) cognitive education in orthodontic practicum and evaluate the teaching effects., Methods: A total of 32 dental students during orthodontic practicum were randomly divided into two groups. One group received traditional teaching method to draft treatment plan, and another group was implemented with DSAS teaching method. Then two groups exchanged. Students were asked to grade both teaching methods and statistical analysis was performed on the scoring results with SPSS 24.0 software package., Results: The scores of the DSAS teaching method was much higher than traditional method, and the difference was statistically significant(P=0.012). Students considered that DSAS teaching method was more "novel and fascinating", and also "convenient for comprehending of orthodontic treatment". Students hoped to popularize the DSAS teaching method in future orthodontic practicum., Conclusions: As a novel teaching method, DSAS is more intuitive and vivid to stimulate students' interest in learning, and it is helpful to improve the effect of orthodontic practical teaching.

The plastisphere is a new ecological niche. Compared to the surrounding water, microbial community composition associated with the plastisphere is known to differ with functional consequences. Here, this study characterized the bacterial and fungal communities associated with four types of plastisphere (polyethylene, polystyrene, polypropylene and polyvinyl chloride) in an estuarine habitat; assessed ecological functions including carbon, nitrogen, phosphorus and sulfur cycling, and determined the presence of antibiotic resistance genes (ARGs) and human pathogens. Stochastic processes dominated the community assembly of microorganisms on the plastisphere. Several functional genera related to nutrient cycling were enriched in the plastisphere. Compared to surrounding water and other plastisphere, the abundances of carbon, nitrogen and phosphorus cycling genes (cdaR, nosZ and chpy etc.) and ARGs (aadA2-1, cfa and catB8 etc.) were significantly increased in polyvinyl chloride plastisphere. In contrast, the polystyrene plastisphere was the preferred substrate for several pathogens being enriched with for example, Giardia lamblia 18S rRNA, Klebsiella pneumoniae phoE and Legionella spp. 23S rRNA. Overall, this study showed that different plastisphere had different effects on ecological functions and health risk in estuaries and emphasizes the importance of controlling plastic pollution in estuaries. Data from this study support global policy drivers that seek to reduce plastic pollution and offer insights into ecological functions in a new ecological niche of the Anthropocene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

α-Boryl ketones are traditionally challenging targets in organic synthesis. Reported herein is a mild and metal-free synthesis of α-boryl ketones via the hydration or oxidation of N -methyliminodiacetyl boronate (B(MIDA))-decorated alkynes. A new hydration system comprised of AcCl and H 2 O in HFIP allows the hydration of arylethynyl B(MIDA)s at room temperature with decent functional group tolerance. An oxidative carbon deletion process of propargylic B(MIDA)s is also developed for the synthesis of aliphatic α-boryl ketones. An intriguing β-boron effect was observed to account for the unique site- and chemoselectivities. The application of the products in the synthesis of borylated heterocycles was demonstrated.

The mechanism and origins of site-selectivity of Rh 2 ( S -tfpttl) 4 -catalyzed C( sp 3 )-H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh 2 ( S -tfpttl) 4 with tert -butylphenol sulfamate TBPhsNH 2 composes a pocket that can access both tertiary and benzylic C-H bonds. The nonactivated tertiary C-H bond was selectively aminated in the presence of an electronically activated benzylic C-H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh-nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive π-π stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C-H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C-H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C-H amination to achieve the amination of the nonactivated tertiary C-H bond.

Rapid spread of antibiotic resistance genes (ARGs) in pathogens is threatening human health. Integrons allow bacteria to integrate and express foreign genes, facilitating horizontal transfer of ARGs in environments. Consumption of raw vegetables represents a pathway for human exposure to environmental ARGs. However, few studies have focused on integron-associated ARGs in the endophytes of raw vegetables. Here, based on the approach of qPCR and clone library, we quantified the abundance of integrase genes and analyzed the diversity and contents of resistance gene cassettes in class 1 integrons from the endophytes of six common raw vegetables. The results revealed that integrase genes for class 1 integron were most prevalent compared with class 2 and class 3 integron integrase genes (1-2 order magnitude, P < 0.05). The cucumber endophytes harbored a higher absolute abundance of integrase genes than other vegetables, while the highest bacterial abundance was detected in cabbage and cucumber endophytes. Thirty-two unique resistance gene cassettes were detected, the majority of which were associated with the genes encoding resistance to beta-lactam and aminoglycoside. Antibiotic resistance gene cassettes accounted for 52.5 % of the functionally annotated gene cassettes, and bla TEM-157 and aadA2 were the most frequently detected resistance cassettes. Additionally, carrot endophytes harbored the highest proportion of antibiotic resistance gene cassettes in the class 1 integrons. Collectively, these results provide an in-depth view of acquired resistance genes by integrons in the raw vegetable endophytes and highlight the potential health risk of the transmission of ARGs via the food chain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study proposed nitrogen addition experiments to analyze the effects of exogenous nitrogen addition on soil fungal diversity in alpine meadow. All the experiments were performed in degraded alpine meadow with two different slopes (gentle slope and steep slope) in Guoluo Prefecture of the Sanjiangyuan Region, and the sequence and analysis of ITS of soil fungi were performed using MiSeq PE250 sequencing technology. Comparative analysis was carried out with three nitrogen addition levels on soil fungal diversity in degraded grassland with different slopes, which included low nitrogen (LN, 2 g·m -2 ), middle nitrogen (MN, 5 g·m -2 ), and high nitrogen (HN, 10 g·m -2 ). The results showed that:① the distribution groups of fungi in the soil were Ascomycota, Basidiomycota, Mortierellomycota, and Glomomycota, and the dominant bacteria was Ascomycota. ② The dominant genera were Mortierella and Archaeorhizomyces , and there were no differences in response to different slopes and nitrogen addition levels. ③ A total of 95 genera ( Gibberellum , Preussia , etc.) were identified and significantly differed between two different slopes ( P <0.05). ④ Bacteria with a relative abundance less than 1% had significant differences in nitrogen addition at different levels on the same slope ( P <0.05). 5 In addition, the analyses of α and β diversities showed that soil fungal community structure was stable under different slopes and nitrogen addition levels. Exogenous nitrogen supplementation significantly improved the relative abundance of non-dominant fungal communities without destroying soil fungal community structure.

Regulation of tumor hypoxia and redox homeostasis is a promising strategy for cancer therapy. Nanocatalytic medicine has played more and more important roles in this field because it can cleverly convert the efficiency and selectivity of catalysis into high therapeutic efficiency. Herein, we developed a platinum(iv)-ruthenium hybrid prodrug, named as Pt-Ru, for efficient chemo-catalytic synergistic therapy of hypoxic tumors. The ruthenium hybridization endowed the Pt(iv) prodrug with multi-enzyme catalytic activity, that is, mimicking catalase (CAT) to generate O 2 in situ , mimicking peroxidase (POD) to produce reactive oxygen species, and mimicking glutathione peroxidase (GPx) to deplete GSH, thus effectively overcoming tumor hypoxia and cisplatin resistance. As a result, Pt-Ru treatment led to a superior anticancer efficacy to cisplatin both in vitro and in vivo . This work suggested redox homeostasis regulation as a tantalizing angle for developing the next generation of platinum drugs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

MiSeq sequencing technology was used to investigate the bacterial compositions and diversities of active patch, non-active patch, recovered patch, and healthy alpine meadows so as to understand the changes in soil bacterial community diversity during altitude change and alpine meadow degradation. The relationship between bacterial diversity and environmental factors was analyzed using redundancy analysis (RDA). The results showed that the dominant bacterial phyla in the soil included Proteobacteria, Actinobacteriota, and Acidobacteriota in the study areas. The dominant bacterial genera that were identified via the MiSeq were RB41, Sphingomonas, and Bradyrhizobium. The relative abundance of these genera decreased with altitude increase and increased with the restoration progress of degraded patches but was significantly lower than that in the alpine meadow ( P <0.05). The abundance of functional bacteria related to carbon fixation in degraded patches was higher than that in the healthy alpine meadow. The bacterial Chao1 index and species number in different types of degraded patches were significantly higher than those in the alpine meadow ( P <0.05). The results of the RDA suggest that biological soil crust coverage and total nitrogen were the main influencing factors on dominant bacterial phyla at the altitude of 4013 m. Biomass, total nitrogen, and pH had a great influence on the dominant bacterial phyla at the altitude of 4224 m. Biomass and total potassium significantly affected the distribution of bacterial genera at the altitude of 4013 m. Sedge coverage and available nitrogen were the main influencing factors on bacterial dominant genera at the altitude of 4224 m. Biological soil crusts and pH had a great influence on bacterial diversities. The bacterial influence factors varied greatly at different altitude areas. Therefore, we should not only pay attention to the effect of alpine meadow degradation but also consider the effect of altitude in the study of bacterial diversity changes.

Since more than 85% of lung cancer cases are non-small cell lung cancer (NSCLC), finding novel agents with anti-tumor activities is meaningful for NSCLC patients. Mitochondria is essential for cellular energy metabolism in cancer, and regulating mitochondrial bioenergetics is emerging as a practical approach for cancer treatment and prevention. The carbazole scaffold is an active structure showing anti-cancer biological activity, and the structural diversity has been expanded through the improvement and optimization of synthesizing methods. To find novel carbazole derivatives with great anti-tumor potential and explore structures variety, we designed and synthesized a series of 9-(pyrimidin-2-yl)-9H-carbazole derivatives based on the previously reported Cp∗Rh(III)/H + tandem catalytic system. With thoroughly bioactivity exploration, we found benzo[d] [1,3]dioxol-5-yl(9-(pyrimidin-2-yl)-9H-carbazol-1-yl)methanone (compound 5n) showed notable activity in disrupting the mitochondrial homeostasis, induced cell cycle arrest and apoptosis in human adenocarcinoma cells, and finally showed anti-tumor activity in an NSCLC-xenograft mice model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Four pairs of stereoisomeric indole alkaloids, (±)-baphicacanthcusines A-D ( 1-4 ), and one new indole alkaloid, baphicacanthcusine E ( 5 ), together with nine known compounds were identified from the leaves of Baphicacanthus cusia . (±)- 1 and - 2 possess an unprecedented skeleton in which two indole moieties are bridged by a phenylpropane unit. (±)- 3 represents the first natural dispiro-oxazolidinone bisoxindoles. The absolute configurations in 1-5 were assigned based on quantum chemical calculations, including the calculated chemical shift with DP4plus analysis, the calculated optical rotation values, and the calculated electronic circular dichroism spectra. A plausible biosynthetic pathway for 1-5 was proposed. Compounds (±)- 1 , (-)- 2 , and 11 exhibited cytotoxicity against MCF-7 cells with IC 50 values of 20.0-78.5 μM.

Introduction: The important role of MYC in tumorigenesis makes it particularly important to design MYC modulators. Over the past decade, researchers have raised a number of strategies for designing MYC modulators, some of which are already in clinical trials. This paper aims to review the patents of MYC modulators., Areas Covered: The important biological relevance of c-MYC and the regulation pathways related to c-MYC are briefly introduced. Base on that, the MYC modulators reported in published patents and references primarily for cancer treatment are outlined, highlighting the structures and biological activities., Expert Opinion: There has been a growing awareness of finding and designing MYC modulators as novel anticancer drugs over recent years. Patents involving the discovery, synthesis, and application of MYC modulators are particularly important for further development in this field. Although finding direct MYC inhibitors or binders is challenging, MYC cannot be simply defined as an undruggable target. There is still substantial evidence proving the concept that MYC modulators can benefit to the treatment of both human hematological malignancies and solid tumors. More efforts should be taken to improve the activity and specificity of MYC modulators.

G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized., Competing Interests: The authors declare no conflict of interest.

A series of Fe/ZSM-5 catalysts with different Fe contents were prepared by impregnation method. The catalysts were characterized by TEM, XRD, H 2 temperature-programed reduction (H 2 -TPR), temperature-programed desorption of ammonia (NH 3 -TPD), and in situ diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS), and the catalytic activity test was also carried out on selective catalytic reduction (SCR) denitration device. Results showed that the single metal iron-supported ZSM-5 catalyst has high deNO x activity in the medium-high temperature range, and the optimal loading of Fe active component is 10 wt%; the deNO x efficiency over 80% at the range of 350-450 °C and 431 °C reaches the maximum of 96.91%. Iron species can be finely dispersed on the surface of the carrier as amorphous oxides, and the crystalline structure of zeolite is retained. The significant redox performance, highly dispersed nanoparticles, and rich Lewis acid sites on the surface of catalyst are favorable for the SCR denitration reaction. Fe/ZSM-5 10 wt% catalyst has rich Lewis acid sites and less B acid sites and Lewis acidic sites play an important role during the reaction. Only Eley-Rideal (E-R) mechanism existed during the NH 3 -SCR reaction process, and there is no denitration reaction being accomplished by L-H mechanism at 150 °C.

Objective: To explore whether interleukin-10 (IL-10) could promote the development of acute respiratory distress syndrome (ARDS) via inhibiting differentiation of bone marrow stem cells (BMSCs) to alveolar type 2 (AT II) epithelial cells., Patients and Methods: 25 ARDS (acute respiratory distress syndrome) patients admitted in our hospital from December 2015 to February 2018 were enrolled. Meanwhile, 25 healthy controls in the same period were selected as control group. Serum level of IL-10 in each subject was detected via ELISA (enzyme-linked immunosorbent assay). BMSCs were isolated and cultured, followed by identification of surface antigens and morphology observation using flow cytometry. For in vitro experiments, expression levels of AT II-related genes induced with or without IL-10 were detected by qRT-PCR (quantitative Real-time polymerase chain reaction) and Western blot, respectively. The culture medium of BMSCs induced with or without IL-10 was collected for detecting expression levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by ELISA., Results: IL-10 was overexpressed in ARDS patients than that of healthy controls. Primary BMSCs were elongated after culturing for 1-3 days. Negative-antigen CD34 (4.32%) and positive-antigen (99.87%) on the surface of BMSCs were identified by flow cytometry. Both mRNA and protein expressions of AT II-related genes increased in a time-dependent manner. ELISA results showed that IL-10 level in cell supernatant decreased with the prolongation of induction days. Moreover, IL-10 intervention downregulated the expressions of AT II-related genes., Conclusions: IL-10 promotes ARDS development via inhibiting cell differentiation of BMSCs to AT II.

The human proto-oncogene neuroblastoma RAS ( NRAS) contains a guanine-rich sequence in the 5'-untranslated regions (5'-UTR) of the mRNA that could form an RNA G-quadruplex structure. This structure acts as a repressor for NRAS translation and could be a potential target for anticancer drugs. Our previous studies found an effective scaffold, the quindoline scaffold, for binding and stabilizing the DNA G-quadruplex structures. Here, on the basis of the previous studies and reported RNA-specific probes, a series of novel p-(methylthio)styryl substituted quindoline (MSQ) derivatives were designed, synthesized, and evaluated as NRAS RNA G-quadruplex ligands. Panels of experiments turned out that the introduction of p-(methylthio)styryl side chain could enhance the specific binding to the NRAS RNA G-quadruplex. One of the hits, 4a-10, showed strong stabilizing activity on the G-quadruplex and subsequently repressed NRAS's translation and inhibited tumor cells proliferation. Our finding provided a novel strategy to discover novel NRAS repressors by specifically binding to the RNA G-quadruplex in the 5'-UTR of mRNA.

Nine new alkylresorcinols, designated as embelialkylresorcinols A-I (1-9), along with five known compounds (10-14) were isolated from the fruits of Embelia ribes. Their structures were elucidated by extensive spectroscopic analysis (1D, 2D NMR and HRESIMS), optical rotation data and modified Mosher method. Notably, embelialkylresorcinols A-H (1-8), possessing double aromatic rings linked with an aliphatic chain, are reported from the genus of Embelia (Myrsinaceae) for the first time. Most of the isolated compounds were evaluated for cytotoxic activity, and the results indicated that compounds 3, 5, 6 and 8 displayed moderate cytotoxicity against three human cancer cell lines (Hep3B, A549 and HCC1806) with IC 50 values ranging from 23.06 to 41.49 μM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Refractory ischemic ulcers that occur in patients with diabetes present a major clinical challenge. Embryonic artery cluster of differentiation 133 + cells (EACCs) may promote the healing of diabetic ulcers; however, the high glucose environment in the diabetic ulcers decreases the survival rate of transplanted EACCs and inhibit their biological function. Furthermore, microcirculation in diabetic ischemic ulcers is impaired, which inhibits the beneficial effect of EACCs. In the current study, the Sirt1 agonist SRT1720 was selected as a therapeutic drug and loaded into a dressing composed of PLGA, collagen and silk (PCSS) formed using electrospinning technology. EACCs were seeded onto the PCSS dressing and this was used to treat diabetic ulcers. The results indicated that SRT1720 promotes the proliferation of EACCs, enhances the secretion of vascular endothelial growth factor A, interluekin 8 and basic fibroblast growth factor, and inhibits the secretion of tumor necrosis factor α. Furthermore, SRT1720 promoted the paracrine function of EACCs and promoted the proliferation and migration of human umbilical vein endothelial cells. PCSS induced the steady release of SRT1720 over a 15-day period and PCSS seeded with EACCs (PCSS-EACCs) were transplanted into the diabetic ischemic ulcers of mice with diabetes. The results of these experiments indicated that angiogenesis and the healing of diabetic ischemic ulcers was significantly improved following the transplantation of PCSS-EACCs. Therefore, PCSS-EACCs may be a novel and effective treatment for diabetic ischemic ulcers.

The specificity of nucleic acids' binders is crucial for developing this kind of drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivatives as c-myc G-quadruplex binding ligands, novel triazole containing benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks. The selectivity toward c-myc G-quadruplex DNA of these novel T-BFQs was significantly improved, together with an obvious increase on binding affinity. Further cellular and in vivo experiments indicated that the T-BFQs showed inhibitory activity on tumor cells' proliferation, presumably through the down-regulation of transcription of c-myc gene. Our findings broadened the modification strategies of specific G-quadruplex stabilizers.

Background: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS., Methods: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation. The intracellular calcium concentration and ROS level were measured using flow cytometry, and the gene expressions of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), encoding sarcoplasmic reticulum Ca2+-ATPase 2a, encoding sodium-calcium exchanger (NCX), and p47phox encoding a subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were examined using real-time quantitative reverse transcription polymerase chain reaction and Western blotting, respectively., Results: We found that the calcium accumulation and ROS generation in the coronary artery smooth muscle cells isolated from either the ischemic or the nonischemic part of the CAL coronary artery vessel were significantly increased irrespective of blood supply (all P < 0.01). Moreover, these were accompanied by the increased expressions of NCX and p47phox, the decreased expression of SERCA2a, and the increased amount of phosphorylated forms of p47phox in NADPH oxidase (all P < 0.05)., Conclusions: Our results demonstrated that the disordered calcium clearance and the increased ROS generation occurred in the coronary artery smooth muscle cells in rats with chronic HF produced by ligation of the left anterior descending coronary artery (CAL), and which was found to be disassociated from blood supply, and the increased generation of ROS in the cells was found to make concomitancy to the increased activity of NADPH oxidase in cytoplasm.

Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC., Competing Interests: Authors F.L., J.-B.Z., H.Y., W.C., M.-Y.Z., X.-X.S. and R.S. are employees of San Valley Biotechnology Inc. in Beijing, China. All other authors declare no conflict of interest.

Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Human umbilical cord mesenchymal stem cells (hUCMSCs) are recognized as candidate progenitor cells for bone regeneration. However, the mechanism of hUCMSC osteogenesis remains unclear. In this study, we revealed that mitogen-activated protein kinases (MAPKs) signaling is involved in hUCMSC osteogenic differentiation in vitro. Particularly, the activation of c-Jun N-terminal kinases (JNK) and p38 signaling pathways maintained a consistent level in hUCMSCs through the entire 21-day osteogenic differentiation period. At the same time, the activation of extracellular signal-regulated kinases (ERK) signaling significantly increased from day 5, peaked at day 9, and declined thereafter. Moreover, gene profiling of osteogenic markers, alkaline phosphatase (ALP) activity measurement, and alizarin red staining demonstrated that the application of U0126, a specific inhibitor for ERK activation, completely prohibited hUCMSC osteogenic differentiation. However, when U0126 was removed from the culture at day 9, ERK activation and osteogenic differentiation of hUCMSCs were partially recovered. Together, these findings demonstrate that the activation of ERK signaling is essential for hUCMSC osteogenic differentiation, which points out the significance of ERK signaling pathway to regulate the osteogenic differentiation of hUCMSCs as an alternative cell source for bone tissue engineering.

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro and subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n = 18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p < 0.01). On the basis of previous studies in vitro and in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.

Phoxonic crystal is a promising material for manipulating sound and light simultaneously. In this paper, we theoretically demonstrate the propagation of acoustic and optical waves along the truncated surface of a two-dimensional square-latticed phoxonic crystal. Further, a phoxonic crystal hetero-structure cavity is proposed, which can simultaneously confine surface acoustic and optical waves. The interface motion and photoelastic effects are taken into account in the acousto-optical coupling. The results show obvious shifts in eigenfrequencies of the photonic cavity modes induced by different phononic cavity modes. The symmetry of the phononic cavity modes plays a more important role in the single-phonon exchange process than in the case of the multi-phonon exchange. Under the same deformation, the frequency shift of the photonic transverse electric mode is larger than that of the transverse magnetic mode.

We aimed to evaluate the feasibility of the application of the nano-hydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffold seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) in bone tissue engineering. We prepared the nHA/CS/PLGA, nHA/PLGA, CS/PLGA, and PLGA scaffolds, and tested their mechanical strength. We analyzed the surface antigen markers of hUCMSCs to determine their capability to differentiate into osteoblasts, chondrocytes, and adipocytes. The growth of hUCMSCs on the four types of scaffold was assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay) and observed using scanning electron microscopy (SEM). Quantitative analysis of alkaline phosphatase (ALP) activity and osteocalcin (OCN) content, as well as the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed. After 21 days, the subcutaneous implantations of the scaffolds samples seeded with hUCMSCs into nude mice were analyzed using immunohistochemical staining. The results showed that the mechanical strength of the nHA/CS/PLGA scaffold was enhanced. Furthermore, the nHA/CS/PLGA scaffolds were the most suitable for the adhesion, proliferation, and osteogenic differentiation of hUCMSCs in vitro and nude mouse subcutaneous implantation. The enhanced osteogenic inductivity of the nHA/CS/PLGA scaffolds for hUCMSCs might result from the addition of nHA and CS., (Copyright © 2013 Society of Plastics Engineers.)

Objective: To investigate the efficiency of perforator pedicled propeller flaps for soft tissue coverage of lower leg and foot defects., Methods: Twenty patients (12 male, 8 females; mean age 28 years, range, 5-75) with soft tissue defects of the lower leg and foot were retrospectively reviewed. Their defects had been repaired with perforator pedicled propeller flaps from September 2011 to October 2013 and included five cases of injuries caused by spokes, four of infection with postoperative skin necrosis, two of dorsal skin defects caused by heavy objects and nine caused by car accidents. The areas of soft tissue defect were from 2 cm × 8 cm to 10 cm × 20 cm. Fifteen cases had terminal branch of the peroneal artery perforator flaps and five posterior tibia artery perforator flaps, flap size ranging from 5 cm × 11 cm to 12 cm × 28 cm. Color Doppler ultrasound was used to locate all perforator vessels, the calibers of which ranged from 0.8 mm to 1.0 mm., Results: The intraoperative coincidence rate of the color Doppler ultrasound was 96.7%. The donor sites were sutured directly in 12 cases and skin grafted in 8. One case had a venous crisis within 24 h that was treated by removal some sutures and drainage. All cases were followed up for 1-18 months; all flaps survived well and pedicles had a satisfactory appearance. The patients were extremely satisfied with the results for repair., Conclusion: Perforator pedicled propeller flaps have the advantages over other pedicle flap of being simple, safe, and effective and not involving vascular anastomosis., (© 2014 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.)

We theoretically demonstrate the existence of simultaneous large complete photonic and phononic bandgaps in three-dimensional dielectric phoxonic crystals with a simple cubic lattice. These phoxonic crystals consist of dielectric spheres on the cubic lattice sites connected by thin dielectric cylinders. The simultaneous photonic and phononic bandgaps can exist over a wide range of geometry parameters. The vibration modes corresponding to the phononic bandgap edges are the local torsional resonances of the dielectric spheres and rods. Detailed discussion is presented on the variation of the photonic and phononic bandgaps with the geometry of the structure. Optimal geometry which generates large phoxonic bandgaps is suggested.

The effects of the Poisson's ratio of the solid host on the band gaps and point defect states of the mixed elastic wave modes in two-dimensional vacuum/solid porous PNCs are studied by numerical simulations. Four typical systems are considered. The four systems are, respectively, (I) the system with a square lattice and circular pores, (II) the system with a hexagonal lattice and circular pores, (III) the system with a square lattice and square pores and (IV) the system with a hexagonal lattice and regular-hexagonal pores. In the latter two systems, with respect to the outer boundaries of the Wigner-Seitz unit cell, the pores rotate 45° and 30°, respectively. Some observable effects of the Poisson's ratio are found in the numerical results. Especially, the variations of the band gap boundaries with the Poisson's ratio exhibit relatively consistent behaviors. With the increase of the Poisson's ratio, the normalized frequency of a band gap boundary generally increases, except that in system (III) the normalized frequency of the upper boundary of the first band gap remains almost unchanged. Detailed interpretations on this phenomenon are given., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Molecular recognition by means of multiple hydrogen bonds is of great importance in biological functions. In this paper, an orotic acid derived bolaamphiphile 1,12-diaminododecane diorotate (DDO) with molecular recognition function moieties was designed. Both self-aggregation behavior and molecular recognition with melamine were extensively examined. This bolaamphiphile itself can form vesicles easily in aqueous solutions at 25 °C. Steady-state fluorescence was used to characterize the detailed molecular recognition process. The fluorescence of melamine was quenched more effectively by the spontaneously formed vesicles than by the monomers of the surfactant. Two mechanisms were involved in the fluorescence quench process. At lower concentration, the fluorescence of melamine was found to be quenched by static complex formation. While at higher concentration, both static and dynamic quenching mechanisms coexisted in interaction process. Thermodynamic parameters measured by isothermal titration calorimetry showed that the free energy (ΔG) is negative, indicating that binding of DDO molecules with melamine is favorable energetically. Hydrogen-bonded interactions contribute comparatively a lot for the DDO monomer binding with melamine; at the higher concentration above its critical aggregation concentration, the dissociation of the aggregates take place and lead to an entropically driven molecular recognition process. As complicated binding sites can be constructed through self-assembly at the vesicle interface rather than simple molecular modules, this bolaamphiphile with the molecular recognition functional group may make it possible to generate well-defined recognition sites to mimic biomolecular receptors. Moreover, the present research will give a guide to design chemosensors for melamine detection based on molecular recognition., (© 2011 American Chemical Society)

Objective: To observe the effects of Tongguan Capsule (TGC) on post-myocardial infarction ventricular remodeling and heart function in rats., Methods: A rat model of acute myocardial infarction (AMI) was established by coronary ligation. Experimental rats were randomized to 4 groups including three model groups (Group A: captopril 5 mg/kg * day, n=7; Group B: TGC 10 g/kg * day, n=7; and Group C: placebo, n=8), and a sham-control group (Group D: blank control, n=6). Animals were treated for 4 weeks. The cardiac function of rats was assessed at the end of the experiment based on left ventricular ejection fraction (LVEF) and left ventricular short axis fractional shortening (LVFS) detected by colored echocardiography; meanwhile, the condition of ventricular remodeling was observed through the levels of left ventricular mass (LVM), plasma aldosterone (ALD), myocardial angiotensin II (Ang II) and myocardial collagen measurements., Results: At the end of the experiment, LVEF and LVFS in Group A and B were improved significantly, while those in Group C were unchanged, the LVEF in Group A, B, C, and D was 0.57+/-0.46, 0.61+/-0.08, 0.36+/-0.55 and 0.76+/-0.02, respectively; and their LVFS was 0.31+/-0.52, 0.34+/-0.04, 0.23+/-0.57 and 0.45+/-0.03, respectively. The difference was statistically significant when comparing the two indexes in Group A and B with those in Group C and D (P<0.05). LVM, levels of plasma ALD and myocardial Ang II were lower in Group A and B than in Group C, but a comparison between Group A and B showed an insignificant difference in lowering LVM and ALD, while the lowering of Ang II was more significant in Group B than in Group A (754.7 +/- 18.7 pg/mL vs 952.6+/-17.6 pg/mL, P<0.05). Morphological examination showed that in Group A and B the swollen myocardial cells had shrunk, with regularly arranged myocardial fibers and decreased collagen proliferation, but the improvements in Group B were more significant., Conclusion: TGC could markedly improve the post-infarction ventricular remodeling and cardiac function in rats, showing that the efficacy was better than or equal to that of captopril.

Objective: To study the therapeutic effects of acupuncture combined with nimodipine for vascular dementia., Methods: Acupuncture was applied at Baihui (GV 20), Shenshu (BL 23), Geshu (BL 17), and the points selected according to the midnight-noon, ebb-flow eight methods of the intelligent turtle, combined with the drug nimodipine. The treatment was continued for 8 consecutive weeks., Results: Of the 30 cases treated, 6 cases were cured, 21 cases improved, and 3 cases failed, with a total effective rate of 90%., Conclusion: Acupuncture at Baihui (GV 20), Shenshu (BL 23), Geshu (BL 17), and the points selected according to the midnight-noon, ebb-flow eight methods of the intelligent turtle combined with the drug nimodipine can yield definite therapeutic effects for vascular dementia.

An isolate of a new tospovirus species, causing concentric zoned ringspots on fruits and necrotic lesions on leaves of infected plants, was characterised based on particle morphology, host range and serological properties. The complete nucleotide sequences of large (L), medium (M), and small (S) RNAs of this virus were found to contain 8919, 4945, and 3279 nts respectively. The L RNA encoded the RNA-dependent RNA polymerase (RdRp) (2885 aa, 332.7 kDa). The M RNA encoded a non-structural (NSm) protein (309 aa, 34.4 kDa) and a viral glycoprotein precursor (Gn/Gc) (1122 aa, 127.4 kDa). The S RNA encoded a non-structural protein (NSs) (459 aa, 51.9 kDa) and the nucleocapsid (N) protein (278 aa, 30.6 kDa). This N protein shared amino acid identities of 80.9% with those of calla lily chlorotic spot virus. Our results suggest that the virus studied here belongs to a new tospovirus species, for which the name tomato zonate spot virus is proposed.

Objective: To observe the changing laws of TCM syndrome type in patients with coronary heart disease (CHD) before and after intervention treatment (IT) and to explore the influence of IT on TCM syndrome type., Methods: The TCM syndrome type of 71 patients with "Chest-Bi" was differentiated before and after percutaneous coronary intervention (PCI) treatment, of which the most common syndrome types were qi deficiency, yang deficiency, yin deficiency, qi stagnation, blood stasis, phlegm, cold coagulation, heat-syndrome, etc., Results: Before PCI treatment, syndrome types of blood stasis (53 cases, 74.6%), qi deficiency (46 cases, 64.8%), and phlegm (28 cases, 39.4%) were the commonest, while there were 12 cases of qi stagnation (16.9%) and 12 cases of cold coagulation (16.9%); One week after PCI treatment, the most commonly seen types were blood stasis (47 cases, 66.2%), qi deficiency (39 cases, 54.9%) and phlegm (23 cases, 32.4%), while qi stagnation (2 cases, 2.8%) and cold coagulation (1 case, 1.4%) were also found; One month after PCI, qi deficiency (47 cases,85.4%), blood stasis (40 cases,72.7%), phlegm (31 cases, 56.4%) were the most commonly seen types. Comparison of the syndrome types between before and after PCI showed that the syndromes of qi deficiency and phlegm were progressively aggravating, while syndromes of qi stagnation and cold coagulation were alleviated after PCI., Conclusion: Although PCI treatment could relieve patients' symptoms of excess in superficiality, it can't radically change the pathogenetic nature of CHD, namely, the deficiency in origin and excess in superficiality, which indicates that one should pay full attention to the importance and necessity of CHD after PCI treatment.